New classifications of axillary lymph nodes and their anatomical-clinical correlations in breast surgery.

BACKGROUND: In the last decade, two research groups, the French group by Clough et al. (Br J Surg. 97:1659-65, 2010) and the Chinese one by Li et al. (ISRN Oncol 2013:279013, 2013), proposed two types of classification of axillary lymph nodes in breast cancer, identifying novel anatomic landmarks for dividing the axillary space in lymph node dissection. MAIN BODY: Knowledge of the exact location of the sentinel node helps to focus the surgical dissection and to reduce the morbidity of sentinel lymph node biopsy procedures, in particular the risk of arm lymphedema, without compromising sensitivity. CONCLUSION: In this article, we aimed at focusing on the clinical impact that the most recent classifications of axillary lymph nodes have obtained in literature, highlighting the importance of defining new demarcations to preserve the axillary lymph nodes as much as possible in breast surgery.

The sequelae of mastectomy and quadrantectomy with respect to the reaching movement in breast cancer survivors: evidence for an integrated rehabilitation protocol during oncological care.

BACKGROUND: Breast cancer (BC) is the most common cancer among women in developed countries. Several types of surgical interventions are commonly used in BC, such as mastectomy and quadrantectomy, followed by radiation or not. Today, BC rehabilitation can help survivors obtain and maintain the highest physical, social, psychological, and vocational functioning possible, within the limits that are created by cancer and its treatments. OBJECTIVE: To verify, before and after a specific rehabilitation protocol treatment, the recovery of the fluidity of the reaching movement. METHODS: Patients after BC surgery were enrolled and assigned by cluster randomization into 2 groups through a block randomization list: mastectomy (Mas) and quadrantectomy (Quad). Evaluation scales (DASH and VAS) were administered, and biomechanical evaluations were performed for each group before treatment (T0 = baseline), at the end of the rehabilitative treatment (T1 = 12 sessions, 2/week), and after 3 months of follow-up (T2). RESULTS: Fifty-nine (Mas group = 29; Quad group = 30) after BC surgery were enrolled. VAS scores improved along the evaluation times at T0-T1 and T0-T2 (p < 0.001), without a statistically significant difference between groups. With regard to the normalized jerk, there was no significant interaction between time group (F = 2.029; p = 0.136). There was a significant decrease between T0-T1 and T1-T2 (F = 60.189; p < 0.001). Velocity improved significantly between T0-T1 and T1-T2 (F = 10.322; p < 0.001). There was a significant interaction for the elbow angle at the end of movement between time and group at T2 (F = 5.022; p = 0.029). CONCLUSION: The integrated, low-intensity, rehabilitative intervention is effective, even if it is not performed in the first period after BC surgery, without any difference between mastectomy and quadrantectomy.

The last week of life of nursing home residents with advanced dementia: a retrospective study.

BACKGROUND: Barriers to palliative care still exist in long-term care settings for older people, which can mean that people with advanced dementia may not receive of adequate palliative care in the last days of their life; instead, they may be exposed to aggressive and/or inappropriate treatments. The aim of this multicentre study was to assess the clinical interventions and care at end of life in a cohort of nursing home (NH) residents with advanced dementia in a large Italian region. METHODS: This retrospective study included a convenience sample of 29 NHs in the Lombardy Region. Data were collected from the clinical records of 482 residents with advanced dementia, who had resided in the NH for at least 6 months before death, mainly focusing on the 7 days before death. RESULTS: Most residents (97.1%) died in the NH. In the 7 days before death, 20% were fed and hydrated by mouth, and 13.4% were tube fed. A median of five, often inappropriate, drugs were prescribed. Fifty-seven percent of residents had an acknowledgement of worsening condition recorded in their clinical records, a median of 4 days before death. CONCLUSIONS: Full implementation of palliative care was not achieved in our study, possibly due to insufficient acknowledgement of the appropriateness of some drugs and interventions, and health professionals' lack of implementation of palliative interventions. Future studies should focus on how to improve care for NH residents.

Longitudinal Physical Activity Change During Hemodialysis and Its Association With Body Composition and Plasma BAIBA Levels.

Rationale: Low physical activity is frequent in end stage renal disease. We evaluated the longitudinal change in physical activity and its barriers in hemodialysis (HD) patients and the association between the patterns of physical activity change, body composition, and beta-aminoisobutyric acid (BAIBA), as circulating myokine. Methods: This is an observational study, where HD patients were considered in a 24-month follow-up. We assessed overtime the change of physical inactivity and its barriers by validated questionnaires, body composition by bioimpedance analysis, muscle strength by hand-dynamometer, and plasma BAIBA levels by liquid chromatography spectrometry. Parametric and non-parametric analyses were performed, as appropriate. Results: Out of the 49 patients studied at baseline, 39 completed the first-year follow-up, and 29 completed the second year. At month 12, active patients had higher intracellular water (ICW) (P = 0.001) and cellular mass (P < 0.001), as well as at month 24 (P = 0.012, P = 0.002; respectively) with respect to inactive. A significant reduction in ICW was shown at month 12 (P = 0.011) and month 24 (P = 0.014) in all patients. The barrier "reduced walking ability" was more frequent in inactive patients with respect to active at month 12 (P = 0.003) and at month 24 (P = 0.05). At month 24, plasma BAIBA levels were higher among active patients with respect to inactive (P = 0.043) and a correlation was seen between muscle strength and ICW (r = 0.51, P = 0.005); normalizing BAIBA per body mass index, we found it lower with respect to baseline (P = 0.004), as well as after correcting per ICW (P = 0.001), as marker of muscle mass. Conclusion: A high prevalence of physical inactivity persisted during a 24-month follow-up in this cohort. We found an association between physical activity and a decline in marker of muscularity and reduced plasma BAIBA levels.

Breast Cancer and Multiple Primary Malignant Tumors: Case Report and Review of the Literature.

Multiple primary malignant neoplasms are multiple tumors with different pathogenetic origin. They may be synchronous or metachronous. The management of these conditions represents an interesting clinical scenario. A crucial aspect is the decision regarding which tumor to treat initially, and how to schedule further treatments according to individual tumor risk. This process involves a multidisciplinary physician team to ensure favorable outcomes. We describe a case report of a female patient affected by primary synchronous tumors of the breast and pectoral skin, which raised a series of diagnostic, etiological and therapeutic issues persuading us to carry out a critical review of the literature.

Investigational drugs for the treatment of cancer cachexia: a focus on phase I and phase II clinical trials.

Introduction: Cachexia is frequent in chronic diseases and especially during cancer development. Multiple definitions of cachexia have been proposed; it may be considered a multifactorial complex syndrome that presents with progressive unintentional weight loss and wasting of muscle mass and adipose tissue. Area covered: This article covers phase-I and phase-II clinical trials of investigational drugs for cancer cachexia. We performed a search on PubMed with keywords as cancer cachexia, phase-I/phase-II trial, drug, identifying articles relevant to this review. Studies were conducted using compounds, including anabolic agents such as ghrelin analogs, selective androgen receptor modulators, as well as anti-inflammatory drugs such as thalidomide, OHR, anti-interleukin antibody, cannabinoids, and omega-3 supplements. We also describe the mechanisms of action of these molecules and their phase-I and phase-II study design. The major outcomes were appetite stimulation, weight gain, improvement of muscle mass and function, modulation of inflammation, and quality of life. Expert opinion: The molecules discussed act on molecular pathways involved in cancer cachexia; they modulate appetite, anabolic effects, inflammation and direct interaction with muscle. Considering the multifactorial aspects of the cachexia syndrome, the combination of these drugs with metabolic and nutritional interventions may represent the most promising therapeutic approach to cancer cachexia.

DHA Oral Supplementation Modulates Serum Epoxydocosapentaenoic Acid (EDP) Levels in Breast Cancer Patients.

INTRODUCTION: The omega-3 polyunsaturated fatty acids, as docosahexaenoic acid (DHA), are considered mediators regulating the resolution of inflammation during cancer and may be associated with better outcomes. Epoxydocosapentaenoic acids (EDPs), metabolites of the DHA, are hypothesized to be responsible for some beneficial effects. In the present study, we aimed to assess the circulating 19,20-EDP levels in breast cancer (BC) patients and in healthy controls before and after DHA oral supplementation and the potential differences in the DHA conversion in 19,20-EDPs between patients with different BC presentations. METHODS: BC patients and healthy controls were supplemented with DHA (algal oil) for 10 days (2 g/day). Blood samples were collected at baseline (T0) and after supplementation (T1) to assess EDP (19,20-EDP) serum levels by liquid chromatography spectrometry. RESULTS: 33 BC patients and 10 controls were studied. EDP values at T0 were not different between patients and controls. At T1, we found an increase in 19,20-EDP levels in BC patients (P < 0.00001) and in controls (P < 0.001), whereas no differences in 19,20-EDPs were present between the two groups; when considering the type of BC presentation, patients with BRCA1/2 mutation showed lower 19,20-EDPs levels with respect to BC patients without the mutation (P = 0.03). According to immunohistochemical subtype, luminal A-like BC patients showed at T1 higher 19,20-EDP levels compared to nonluminal A (P = 0.02). CONCLUSIONS: DHA oral supplementation was associated with increased 19,20-EDP serum levels in BC patients, independent of the type of BC presentation, and in controls. Patients carrier of BRCA1/2 mutation seem to possess lower ability of DHA epoxidation, whereas luminal A-like BC patients showed higher EDP conversion. This behavior should be tested in a larger population.

PD-1 Ligand Expression in Epithelial Thyroid Cancers: Potential Clinical Implications.

The new immunotherapy targeting the programmed cell death 1 (PD-1) receptor and its cognate ligand PD-L1 has renewed hopes of eradicating the most difficult human cancers to treat. Among these, there are the poorly differentiated and anaplastic thyroid cancers, unresponsive to all the therapies currently in use. In the present review we will summarize information regarding the expression of PD-L1 in the different thyroid cancer histotypes, its correlation with clinicopathological features, and its potential prognostic value. Then, we will evaluate the available data indicating the PD-1/PD-L1 axis as a promising target for thyroid cancer therapy.

Breast cancer subtypes affect the nodal response after neoadjuvant chemotherapy in locally advanced breast cancer: Are we ready to endorse axillary conservation?

We evaluated the impact of breast cancer subtypes on pathologic complete response (pCR) in 181 patients with positive nodes undergoing neoadjuvant chemotherapy (NAC). After NAC, patients underwent surgery, with sentinel lymph node biopsy (SLNB) or axillary dissection (ALND). In 28.2% of cases a pCR was achieved, with the highest rate in Her2+ and triple negative tumors. Overall, nodal pCR was more frequent than breast pCR (P = 0.003) with higher percentages in Her2+ and LLB-Her2+ (P < 0.05). In the Her2+ group, nodal pCR was observed only with breast pCR. Thus, in Her2+ tumors, breast pCR predicts node pCR, supporting the use of SLNB in this subgroup to stage the axilla avoiding ALND.

Morphological and Semiquantitative Kinetic Analysis on Dynamic Contrast Enhanced MRI in Triple Negative Breast Cancer Patients.

RATIONALE AND OBJECTIVES: The aim of this study was to retrospectly investigate the association between different breast cancer (BC) immunohistochemical subtypes and morphological and semiquantitative kinetic analysis on breast magnetic resonance imaging (MRI) performed before surgery treatment. Specifically we aimed to assess MRI features of triple-negative breast cancer (TNBC) compared to the other BC subtypes (nTNBC). MATERIALS AND METHODS: Patients undergone to breast MRI and then diagnosed with BC by core-needle biopsy were included. The MRI morphological and kinetic features were studied. Parametric and non-parametric tests were used, as appropriate. RESULTS: Seventy-five BC patients were considered, 30 patients included in TNBC Group and 45 patients included in nTNBC Group. We found in TNBC Group a greater mean lesion size (P <0.001), a rim enhancement imaging (P=0.003), and a higher intratumoral signal intensity on T2-weighted images (P=0.03) with respect to nTNBC Group. We noticed that TNBC patients presented a lower grade of BPE when compared to the nTBC Group (P< 0.02). TNBC Group showed lower EPeak values (P=0.003) and higher SER values (P=0.02) with respect to the nTNBC Group. In addition, stratifying kinetics parameters according to the tumor grade, the TNBC Group presented higher tumor grade (G3) (P< 0.005) and this subgroup had higher SER values when compared to TNBCs showing a lower tumor grade (G1 and G2) (P=0.03). CONCLUSION: After validation by large-scale studies, the morphological and semiquantitative kinetic analysis on dynamic contrast enhanced MRI may help in the pretreatment risk stratification of patients with TNBC and in evidence-based clinical decision support.

The Impact of Nursing Homes Staff Education on End-of-Life Care in Residents With Advanced Dementia: A Quality Improvement Study.

CONTEXT: End-of-life care in nursing homes (NHs) needs improvement. We carried out a study in 29 NHs in the Lombardy Region (Italy). OBJECTIVES: The objective of this study was to compare end-of-life care in NH residents with advanced dementia before and after an educational intervention aimed to improving palliative care. METHODS: The intervention consisted of a seven-hour lecture, followed by two 3-hour meetings consisting of case discussions. The intervention was held in each NH and well attended by NH staff. This multicenter, comparative, observational study included up to 20 residents with advanced dementia from each NH: the last 10 who died before the intervention (preintervention group, 245 residents) and the first 10 who died at least three months after the intervention (postintervention group, 237 residents). Data for these residents were collected from records for 60 days and seven days before death. RESULTS: The use of "comfort hydration" (<1000 mL/day subcutaneously) tended to increase from 16.9% to 26.8% in the postintervention group. The number of residents receiving a palliative approach for nutrition and hydration increased, though not significantly, from 24% preintervention to 31.5% postintervention. On the other hand, the proportion of tube-fed residents and residents receiving intravenous hydration decreased from 15.5% to 10.5%, and from 52% to 42%, respectively. Cardiopulmonary resuscitations decreased also from 52/245 (21%) to 18/237 (7.6%) cases (P = 0.002). CONCLUSION: The short educational intervention modified some practices relevant to the quality of end-of-life care of advanced dementia patients in NHs, possibly raising and reinforcing beliefs and attitudes already largely present.

Improving Weight Loss by Combination of Two Temporary Antiobesity Treatments.

BACKGROUND: It is generally accepted that the efficacy with an intragastric balloon decreases after the first 4 months of treatment. Aim of this study is to evaluate if the association of a very low-calorie ketogenic diet (VLCKD) can improve the results in terms of weight loss parameters and co-morbidities, as compared to usually prescribed low-calorie diet (LCD). METHODS: For the present study (January 2016-June 2017), 80 patients (20 M/60 F, mean age 37.8 ± 6.1 years; excess weight 56 ± 10 kg; mean BMI 37.2 ± 3.8 kg/m2) underwent Orbera positioning. After 4 months, they were randomized into two groups according to the type of treatment: group A (Bioenterics intragastric balloon - Orbera + VLCKD) (n = 40), and group B (Orbera + LCD) (n = 40). RESULTS: All patients completed the study with good adherence to diet therapy treatment allocation. After the 6-month treatment period, at time of Orbera removal, mean weight loss was 19 kg and 12 kg in groups A and B respectively (p < 0.05). Mean BMI was 28.9 ± 2.8 and 31.6 ± 3.1 kg/m2 (p < 0.05), and %EWL was 33.1 ± 3.3 and 21.1 ± 2.9 (p < 0.05) in groups A and B respectively. During the last 2 months in group A, the mean weight loss was 8 kg, while in Group B, the main weight loss was 3 kg (p < 0.001). The VLCKD treatment induced a more significant reduction of major comorbidities related to metabolic syndrome. CONCLUSIONS: This study clearly indicates the efficacy of the prescription of very low-calorie ketogenic diet improving the efficacy of intragastric balloon positioning.

CTLA-4 and PD-1 Ligand Gene Expression in Epithelial Thyroid Cancers.

The dysregulation of PD-1 ligands (PD-L1 and PD-L2) and CTLA-4 ligands (CD80 and CD86) represents a tumor strategy to escape the immune surveillance. Here, the expression of PD-L1, PD-L2, CD80, and CD86 was evaluated at the mRNA level in 94 patients affected by papillary thyroid carcinoma (PTC) and 11 patients affected by anaplastic thyroid carcinoma (ATC). Variations in the mRNAs in PTC patients were then correlated with clinicopathological features. The expression of all genes was deregulated in PTC and ATC tissues compared to normal tissues. In particular, the downregulation of CD80 was observed above all in ATC. In addition, the increased expression of CD80 associated with longer disease-free survival in PTC. Higher expression of PD-L1 associated with the classical histological variant and with the presence of BRAFV600E mutation in PTC. The increased PD-L2 expression correlated with BRAFV600E mutation and lymph node metastasis, while its lower expression correlated with the follicular PTC variant. The latter was also associated with the CD80 downregulation, which was also related to the absence of lymph node metastasis. In conclusion, we documented the overall dysregulation of PD-1 and CTLA-4 ligands in PTC and ATC tissues and a possible prognostic value for CD80 gene expression in PTC.

Thyroid diseases and skin autoimmunity.

The skin is the largest organ of the body, at the boundary with the outside environment. Primarily, it provides a physical and chemical barrier against external insults, but it can act also as immune organ because it contains a whole host of immune-competent cells of both the innate and the adaptive immune systems, which cooperate in eliminating invading pathogens following tissue injury. On the other hand, improper skin immune responses lead to autoimmune skin diseases (AISD), such as pemphigus, bullous pemphigoid, vitiligo, and alopecia. Although the interplay among genetic, epigenetic, and environmental factors has been shown to play a major role in AISD etiology and progression, the molecular mechanisms underlying disease development are far from being fully elucidated. In this context, epidemiological studies aimed at defining the association of different AISD with other autoimmune pathologies revealed possible shared molecular mechanism(s) responsible for disease progression. In particular, over the last decades, a number of reports have highlighted a significant association between thyroid diseases (TD), mainly autoimmune ones (AITD), and AISD. Here, we will recapitulate the epidemiology, clinical manifestations, and pathogenesis of the main AISD, and we will summarize the epidemiological evidence showing the associations with TD as well as possible molecular mechanism(s) underlying TD and AISD pathological manifestations.

Pneumonia in Nursing Home Patients With Advanced Dementia: Decisions, Intravenous Rehydration Therapy, and Discomfort.

BACKGROUND: Comfort may be an appropriate goal in advanced dementia. Longitudinal studies on physician decision-making and discomfort assessed by direct observation are rare, and intravenous rehydration therapy is controversial. METHODS: To assess treatment decisions and discomfort in patients with advanced dementia and pneumonia and to compare by intravenous rehydration therapy, we used data from the observational multicenter Italian End of Life Observatory-Prospective Study On DEmentia patients Care. We analyzed 109 episodes of pneumonia, which involved decisions in 77 nursing home patients with Functional Assessment Staging Tool stage 7. We assessed decisions, decision-making, and treatments every fortnight. Trained observers assessed discomfort with the Discomfort Scale-Dementia Alzheimer Type (DS-DAT). RESULTS: Most decisions referred to treatment with antibiotics (90%; 98 of 109) and intravenous rehydration therapy (53%; 58 of 109), but hospitalization was rare (1%). Selecting decisions with antibiotics, with rehydration therapy, the prognosis was more frequently <15 days (34% vs 5% without rehydration therapy; P = .001), and a goal to reduce symptoms/suffering was more common (96% vs 74%; P = .005) while there was no difference in striving for life prolongation (a minority). With rehydration therapy, the decision was more often discussed with family rather than communicated only. Mean DS-DAT scores over time proximate to the first decision ranged between 9.2 and 10.5. CONCLUSIONS: Italian nursing home patients with advanced dementia and pneumonia frequently received invasive rehydration therapy in addition to antibiotics, however, mostly with a palliative intent. Discomfort was high overall and symptom relief may be improved. Relations between invasive rehydration therapy and discomfort need further study.

Magnetic Resonance Imaging after Breast Oncoplastic Surgery: An Update.

Breast-oncoplastic surgery, allowing local tumor control and a better cosmetic outcome, is oncologically safe when applied to early-stage breast cancer. Breast cancer recurrence following conservative therapy may occur during the first 5 years after treatment, with a peak incidence after 2 years. Therefore, during the follow-up period, patients undergo a series of ultrasound (US) and mammographic examinations. However, after surgery and radiation therapy, several modifications occur in the treated breast, causing difficulties in image interpretation, especially when local recurrence is suspected. Although not included in routine follow-up, magnetic resonance imaging (MRI) is often used in clinical practice, being considered more sensitive than the conventional imaging examinations in discriminating between postsurgical tissue modifications and tumor recurrence. In this review article, we analyze expected and pathologic breast MRI findings after conservative oncoplastic surgery compared to US and mammographic findings in order to distinguish local recurrence and avoid potential pitfalls in image interpretation.

Lipofilling Outcomes Mimicking Breast Cancer Recurrence: Case Report and Update of the Literature.

Breast lipofilling uses autologous fat grafting to correct breast defects after radical or conservative surgery. After early concerns regarding its application in reconstruction after breast cancer (BC), in 2009 the American Society of Plastic Surgeons formed a task force to assess the indications, safety and efficacy of autologous fat grafting. We report the case of a woman who came to our attention for a painful swelling of the left breast. She had undergone breast-conserving therapy for BC, followed by lipofilling. The breast ultrasound (US) examination showed diffuse structural alteration and multiple hypoechoic areas with acoustic shadowing, mainly localized in the subcutaneous tissue. After pharmacological treatment and short-term follow-up US examination, considering the persistence of the clinical symptoms and structural alterations, we performed contrast-enhanced magnetic resonance imaging, that showed multiple enhancing areas in the left breast. Suspecting local tumor recurrence, we carried out US-guided breast core-biopsy, whose histological examination documented liponecrosis. This observation raised a series of diagnostic and therapeutic issues highlighting the diagnostic pitfalls that the radiologist may encounter during the evaluation of patients who have undergone BC surgery and breast reconstruction through lipofilling.

Effect of Oral Docosahexaenoic Acid (DHA) Supplementation on DHA Levels and Omega-3 Index in Red Blood Cell Membranes of Breast Cancer Patients.

Rationale: Docosahexaenoic acid (DHA) in cell membrane may influence breast cancer (BC) patients' prognosis, affecting tumor cells sensitivity to chemo- and radio-therapy and likely modulating inflammation. The possibility of identifying BC patients presenting with low DHA levels and/or low ability of DHA incorporation into cell membrane might help to treat this condition. Methods: We enrolled BC patients and healthy controls, recording their seafood dietary intake. DHA in form of algal oil was administered for 10 consecutive days (2 g/day). Blood samples were collected at baseline (T0) and after 10 days of supplementation (T1) to assess DHA, omega-3 index, as the sum of DHA + eicosapentaenoic acid (EPA), in red blood cells (RBC) membranes and plasma tumor necrosis factor-alpha and interleukin-6 levels. Pre- and post-treatment fatty acid profiles were obtained by gas-chromatography. Parametric and non-parametric tests were performed, as appropriate, and P-value < 0.05 was considered statistically significant. Results: Forty-three women were studied, divided into 4 groups: 11 patients with BRCA1/2 gene mutation (M group), 12 patients with familiar positive history for BC (F group), 10 patients with sporadic BC (S group), and 10 healthy controls (C group). DHA and omega-3 index increased from T0 to T1 in the 3 groups of BC patients and in controls (P < 0.001). No difference was found in DHA incorporation between each group of BC patients and between patients and controls, except for M group, which incorporated higher DHA levels with respect to controls (ß = 0.42; P = 0.03). No association was documented between cytokines levels and DHA and omega-3 index at baseline and after DHA supplementation. Independent of the presence of BC, women considered as "good seafood consumers" showed at baseline DHA and omega-3 index higher with respect to "low seafood consumers" (P = 0.04; P = 0.007, respectively). After supplementation, the increase in DHA levels was greater in "low seafood consumers" with respect to "good seafood consumers" (P < 0.0001). Conclusion: DHA supplementation was associated with increased DHA levels and omega-3 index in RBC membranes of BC cancer patients, independent of the type of BC presentation, and in controls. BRCA1/2 mutation, as well as low seafood consuming habits in both BC patients and healthy controls, seem to be associated with greater ability of DHA incorporation. Larger samples of BC patients are necessary to confirm our observation.

Cancer stem cells as functional biomarkers.

According to the American Association of Cancer Research (AACR), a Cancer Stem Cell is a cell within a tumor that possesses the capacity to self-renew and to cause the heterogeneous lineages of cancer cells that constitutes the tumor [1]. Cancer Stem Cells (CSCs) are involved in the metastatic process, in the resistance to therapeutic treatments of many types of human cancers and consequently in the onset of recurrences. Numerous translational studies have been conducted to understand CSC characteristics and evaluate association between CSC-related biomarkers and clinical outcomes. The CSC theory can explain also a tumor relapse after that a tumor has been completely surgically removed (R0 macroscopical zero residual resection) or after an apparently complete response to chemotherapy. CSCs, in fact, showed a marked ability to reduce intracellular accumulation of chemotherapic agents by active drug extrusion, increased chemoresistance and survival, as well as elevated membrane transporter activity. In addition, it is possible that these cancer stem cells may nest in the "secured" (niche) sites of our body, where they may remain undisturbed for a long time, even years, until a stimulus arrives to awaken them, causing the disease to resume. CSCs, in fact, are able to use a variety of cellular pathways to survive to anticancer treatments. More recently CSCs have been described in several solid tumors, expressing specific biomarkers. Another field of research should be focused on the realization of diagnostic instruments to follow up patients after R0 surgical resection or after a complete response for an early detection and management of relapse and metastasis.

Omega-3 Polyunsaturated Fatty Acids in Critical Illness: Anti-Inflammatory, Proresolving, or Both?

Prognosis and outcomes of critically ill patients are strictly related with inflammatory status. Inflammation involves a multitude of interactions between different cell types and chemical mediators. Omega-3 polyunsaturated fatty acids (PUFAs), mainly represented by eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are able to inhibit different pathways including leukocyte chemotaxis, adhesion molecule expression and interactions, and production of inflammatory cytokines, through the action of specialized proresolving mediators (SPMs). SPMs from omega-6 fatty acids, such as lipoxins, and from omega-3 fatty acids such as resolvins, protectins, and maresins, act in reducing/resolving the inflammatory process in critical diseases, stimulating the phases of resolution of inflammation. In this light, the resolution of inflammation is nowadays considered as an active process, instead of a passive process. In critical illness, SPMs regulate the excessive posttrauma inflammatory response, protecting organs from damage. This review focuses on the role of omega-3 PUFAs as pharma nutrition agents in acute inflammatory conditions, highlighting their effects as anti-inflammatory or proresolving agents.